The overall objective of this NCVDG is to develop new generations of formulations of synthetic immunogens or new HIV immunogens derived from synthetic peptide subunit motifs that will induce long-lasting anti-HIV protective immune responses both systemically and at mucosal surfaces against a wide variety of HIV stains. Most importantly, the projects in this NCVDG will use HIV synthetic peptides as experimental immunogens to answer critical scientific questions related to HIV vaccine development. Specific objective of the NCVDG are: 1) to define optimal formulations of multivalent HIV peptide subunit immunogens that will induce mucosa anti-HIV neutralizing antibody responses and anti-HIV MHC Class I- restricted CTL responses, 2) to define new HIV peptide motif subunit immunogens that mimic the secondary structures of HIV envelope neutralizing determinants based on the new technology of RNA in vitro selection, 3) to define new adjuvant formulations for HIV subunits based on new insights into antigen presentation and the molecular basis of memory T and B cells induction, 4) to define the MHC Class II restriction elements i rhesus monkeys and humans that are responsible for T helper (Th) cell activation by SIV and HIV Th protein epitopes, and 5) to express multiple HIV peptide subunit immunogenic regions containing Th, CTL, B cell neutralizing epitopes in Salmonella sp. or expressed on the surface of Salmonella as flagellin fusion proteins. Thus, this NCVDG will bring together outstanding basic scientists utilizing novel and important technologies to design new HIV subunit immunogens, and will use formulations for HIV vaccine candidates.